舒洛地特对糖尿病大鼠尿白蛋白排泄率及肾脏转化生长因子-β1表达的影响  

Effects of sulodexide on urinary albumin excretion rate and expression of transforming growth factor-β1 in renal tissue of diabetic rats

作　　者：林可意[1] 曾龙驿[1] 舒同[1] 穆攀伟[1] 江柏泉[1] 

机构地区：[1]中山大学附属第三医院内分泌科,广州,510630

出　　处：《中华糖尿病杂志》2009年第3期-,共5页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的 探讨舒洛地特对链脲佐菌素诱导的糖尿病大鼠尿白蛋白排泄率及肾脏转化生长因子-β1 mRNA和蛋白表达的影响.方法 33只健康8周龄雄性SD大鼠采用随机数字表法分为健康对照组(n=11)、糖尿病组(n=11)及舒洛地特干预组(n=11).糖尿病组和舒洛地特干预组空腹10 h后一次性腹腔内注射链脲佐菌素溶液(65 mg/kg),健康对照组注射等量生理盐水.72 h后尾静脉空腹血糖>16.7 mmol/L且持续3 d视为造模成功,其中糖尿病组成模大鼠9只,舒洛地特干预组成模大鼠10只.舒洛地特干预组给予10 mg·kg-1·d-1舒洛地特灌胃,糖尿病组和健康对照组给予等量生理盐水灌胃,共12周.用药结束后次晨测定24 h尿白蛋白排泄率,留取肾脏组织作转化生长因子-β1免疫组织化学染色,应用逆转录-聚合酶链反应(RT-PCR)测定其mRNA表达水平.采用单因素方差分析及SNK或LSD检验进行统计学分析.结果 24 h尿白蛋白排泄率糖尿病组平均为363μg/min,舒洛地特干预组为151μg/min,健康对照组为26 μg/min,差异有统计学意义(F=93.93,P<0.01).糖尿病组肾脏组织转化生长因子-β1 mRNA的表达量为3.11±0.84,舒洛地特干预组为0.99±0.27,健康对照组为0.44±0.13,差异有统计学意义(F=80.43,P<0.01).肾脏组织转化生长因子-β1蛋白免疫组织化学染色在糖尿病组着色深且广泛,舒洛地特干预组较糖尿病组染色浅,与健康对照组相近.结论 舒洛地特可降低尿白蛋白排泄率,下调肾脏组织转化生长因子-β1 mRNA及蛋白的表达,从而发挥肾脏保护作用.Objective To investigate the effects of sulodexide on 24-h urinary albumin excretion rate (UAER) and the mRNA or protein expression of transforming growth factor-β1 (TGF-β1) in diabetic rats induced by streptozotocin. Methods Thirty-three healthy eight-week-old male Sprague Dawley (SD) rats were randomly divided into the normal control group (n = 11), diabetic group (n = 11), and sulodexide intervention group (n = 11). The last two groups were injected with streptozotocin (65 mg/kg) at abdominal cavity while the normal control rats were injected with saline after 10 hours' fasting. When fasting blood glucose was > 16.7 mmol/L for 72 h, the rats were confirmed to be patterned successfully. Nine rats in the diabetic group and 10 rats in the sulodexide group entered the study. The dose of sulodexide was 10 mg·kg-1·d-1, and the other two groups were administrated with comparative normal saline for 12 weeks. Overnight urine was collected to assess 24-h UAER after 12 weeks' treatment, and the renal sections were handed by immunohistochemical staining and the expression of TGF-β1 mRNA was detected by RT-PCR. One-way analysis of variances and SNK or LSD test were used for data analysis. Results 24-h UAER were average 363 μg/min in the diabetes control group, 151 μg/min in the sulodexide intervention group, and 26 μg/min in the normal control group (F =93.93 ,P <0.01). The expression of TGF-β1 mRNA were 3.11±0.84 in the diabetic group, 0.99±0.27 in the sulodexide intervention group, and 0.44±0.13 in the normal control group (F = 80.43, P < 0.01). The expression of TGF-β1 protein was most obvious in the endochylema of the renal tubule epithelium cells in diabetic rats, which was attenuated markedly by sulodexide. Conclusions Sulodexide may play an important role in renoprotection by decreasing UAER and down-regulating the expression of TGF-β1 mRNA and protein of the renal tissues in diabetic rats.

关 键 词：糖尿病 白蛋白类 转化生长因子-Β 舒洛地特 

分 类 号：R587.2[医药卫生—内分泌]